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丝裂原活化蛋白激酶激活的蛋白激酶2（MK2）抑制剂作为炎症性疾病的治疗方法

Inhibitors of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK2) as Treatment for Inflammatory Diseases.

作者信息

Abdel-Magid Ahmed F

机构信息

PI Health Sciences, 100 Jade Park, Chelsea, Alabama 35043, United States.

出版信息

ACS Med Chem Lett. 2024 Aug 23;15(9):1421-1423. doi: 10.1021/acsmedchemlett.4c00393. eCollection 2024 Sep 12.

DOI:10.1021/acsmedchemlett.4c00393
PMID:39291023
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11403732/
Abstract

The invention in this patent application relates to 9,10,11,12-tetrahydro-8-[1,4]diazepino[5',6':4,5]thieno[3,2-]quinolin-8-one derivatives represented herein generally by Formula . These compounds are inhibitors of MK2 kinases and may provide useful treatments for MK2-mediated diseases or disorders such as autoimmune disorders, chronic or acute inflammatory disorders, autoinflammatory disorders, fibrotic disorders, metabolic disorders, neoplasia, or cardiovascular or cerebrovascular disorders.

摘要

本专利申请中的发明涉及通式所示的9,10,11,12-四氢-8-[1,4]二氮杂卓并[5',6':4,5]噻吩并[3,2-]喹啉-8-酮衍生物。这些化合物是MK2激酶的抑制剂，可用于治疗MK2介导的疾病或病症，如自身免疫性疾病、慢性或急性炎症性疾病、自身炎症性疾病、纤维化疾病、代谢紊乱、肿瘤形成或心血管或脑血管疾病。

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本文引用的文献

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Small molecule targeting of the p38/Mk2 stress signaling pathways to improve cancer treatment.靶向 p38/Mk2 应激信号通路的小分子改善癌症治疗。
BMC Cancer. 2023 Sep 23;23(1):895. doi: 10.1186/s12885-023-11319-x.
2
Selective Inhibition of the MK2 Pathway: Data From a Phase IIa Randomized Clinical Trial in Rheumatoid Arthritis.MK2 通路的选择性抑制：来自类风湿关节炎 IIa 期随机临床试验的数据。
ACR Open Rheumatol. 2023 Feb;5(2):63-70. doi: 10.1002/acr2.11517. Epub 2023 Jan 5.
3
Diversity and versatility of p38 kinase signalling in health and disease.p38 激酶信号在健康和疾病中的多样性和多功能性。
Nat Rev Mol Cell Biol. 2021 May;22(5):346-366. doi: 10.1038/s41580-020-00322-w. Epub 2021 Jan 27.
4
MAPKAPK2: the master regulator of RNA-binding proteins modulates transcript stability and tumor progression.MAPKAPK2：RNA 结合蛋白的主调控因子调节转录本稳定性和肿瘤进展。
J Exp Clin Cancer Res. 2019 Mar 8;38(1):121. doi: 10.1186/s13046-019-1115-1.
5
Novel Therapeutic Potential of Mitogen-Activated Protein Kinase Activated Protein Kinase 2 (MK2) in Chronic Airway Inflammatory Disorders.丝裂原活化蛋白激酶激活的蛋白激酶 2（MK2）在慢性气道炎症性疾病中的新治疗潜力。
Curr Drug Targets. 2019;20(4):367-379. doi: 10.2174/1389450119666180816121323.